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ATAC-seq for Characterizing Host and Pathogen Genome Accessibility During Virus Infection
Dawei Liu1, Timothy R Howard1, Ileana M Cristea2
1Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Methods in Molecular Biology (Clifton, N.J.)
|November 15, 2024
Summary
This study details an optimized Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) method for analyzing host and viral genome accessibility during infection. The method revealed host factor IFI16 reduces herpes simplex virus type I (HSV-1) genome accessibility.
Area of Science:
- Molecular Biology
- Epigenetics
- Virology
Background:
- Chromatin regulation is crucial for dynamic gene expression in biological processes and diseases.
- Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) maps genome-wide chromatin accessibility.
- ATAC-seq is valuable for studying viral and bacterial infections, revealing pathogen replication and host defense insights.
Purpose of the Study:
- To describe an optimized ATAC-seq method for simultaneous analysis of host and viral genome accessibility.
- To investigate virus-host interactions by detecting structural changes on viral genomes.
- To provide a versatile tool for research involving foreign DNA introduction.
Main Methods:
- Utilized an optimized ATAC-seq protocol to assess chromatin accessibility.
- Applied the method to study infections with viral pathogens, specifically herpes simplex virus type I (HSV-1).
- Investigated the role of host antiviral factors in modulating viral genome accessibility.
Main Results:
- Demonstrated a systematic decrease in herpes simplex virus type I (HSV-1) genome accessibility during infection.
- Identified the host antiviral factor, interferon-gamma inducible protein 16 (IFI16), as mediating this decrease.
- Showcased the method's ability to provide mechanistic insights into virus-host interactions.
Conclusions:
- The optimized ATAC-seq protocol effectively characterizes chromatin accessibility changes in both host and viral genomes.
- IFI16 plays a role in restricting HSV-1 replication by reducing viral genome accessibility.
- This adaptable ATAC-seq method is a valuable tool for diverse research areas involving foreign DNA and host-pathogen interactions.

